Recently, I have characterized a transplantable rat pheochromocytoma as a model system in which to study the regulation of catecholamine metabolism. Incubation of cell suspensions prepared from this tumor in media containing 56 mM K ions results in an increase in the synthesis of norepinephrine from C14-tyrosine in these cells. It appears that stimulation by 56 mM K ions causes an activation of tyrosine 3-monooxygenase within the cells. During the next year, I will carry out studies designed to elucidate the mechanism of this stimulation-induced activation of tyrosine 3-monooxygenase. Tyrosine 3-monooxygenase will be assayed in extracts prepared from control and stimulated pheochromocytoma cells, and the enzymes from the two sources $ will be compared with respect to their maximal velocities, their Kms for tyrosine and for pteridine cofactor, and their ability to be activated by Ca2 ions and by cyclic adenosine 3',5'-monophosphate. I have also recently developed radioisotopic methods for estimating the pH and membrane potential of adrenal medullary chromaffin granules. During the next year, I plan to use these methods, as well as fluorometric methods, to estimate the pH and membrane potential of chromaffin granules incubated in vitro. BIBLIOGRAPHIC REFERENCES: Dolais-Kitabgi, J., and Perlman, R.L., The Stimulation of Catecholamine Release from Chromaffin Granules by Valinomycine, Mol. Pharmacol., 11, 745-750 (1975). Hochman, J., and Perlman, R.L., Catecholamine Secretion by Isolated Adrenal Cells, Biochim. Biophys. Acta., 421, 168-175 (1976).